Diffuse Optical Imaging (DOI) allows us access to the hemodynamic response in tissue. It has been shown that we can, by detecting the effects of neuro-vascular coupling, relate this to functional events in the brain. Existing technologies in DOI are limited by a number of factors, but most strongly by the absence of viable clinical applications where they may be applied. Originally we were targeting young epilepsy sufferers who have had radical hemispherectomies, and veterans (at the upper end of the pediatric population) with penetrating Traumatic Brain Injury (TBI). This year we have, through our continuing outreach, identified a third key population, Autistic Spectrum Disorder (ASD) patients. These patients are low-functioning and typically pediatric populations. Over the course of the 2010 fiscal year we have developed our collaborations, secured a patent for one of our novel instrument ideas, and had several presentations accepted at the Society for Neuroscience. We are assembling a variety of instruments both in the lab (through our collaborators at Drexel) and at our other collaborators lab in Georgetown. The latter is a DOI instruments combined with EEG. Clinically we are now commencing initial testing with healthy volunteers. We are awaiting the protocol number for our newly approved IRB through NICHD to begin testing on our prototype systems here at NICHD. To conduct functional brain imaging experiments, we have developed a number of cognitive tasks (event complexity judgment task, a verbal working memory task, and a multi-task) in E-prime software. The timing of the presentation of each stimulus will be accurately recorded which will be used in data analysis. We have also worked on data processing techniques to extract the brain hemodynamic response from the optical data. Initial experiments were performed using the event complexity task in collaboration with Georgetown. Principal component analysis (PCA) and independent component analysis (ICA) have been applied to the data to remove the noise and motion artifact components. Corresponding extracted hemodynamic responses validate the technique as they correlate with the results of previous fMRI studies. In addition, with collaborators at NIMH, we are currently discussing suitable functional studies useful to ASD patients, and once we have initial data on healthy volunteers, we will produce a study on ASD patients, either in a young adult or pediatric population. Theoretically we are currently working on a variety of approaches for handling the shortcomings of current DOI techniques. Our primary focus at the moment is addressing the issue of atlasing and registration for DOI. This area is a hot topic of research but unlike MRI where Talairach and MNI atlases have become de facto standards DOI has no such standard approach. Part of this is the absence of certainty in reconstruction methodologies and part is the issue of co-registering data. We have been working on better quantitation and localization of optical signals as part of the project. Our current focus though has been on readdressing atlasing and registration by mapping data to a different co-ordinate basis. We are currently finishing a paper based on the principle of moving optical data into a polar/spherical basis (which is more natural to its sensitivity and resolution). By doing so we can directly register data in the 3D volume based upon an effective registration of the 2D surface manifold. This method will also combine with work we are developing on describing the sensitivity of optical imaging in fractal dimensions. This will combine to allow us to evolve much more sophisticated probabilistic functional atlases of the human brain for DOI. Our collaboration with NINDS continues to develop a new fiber based imager to add to our selection of devices for comparison and contrast of DOI techniques. Also we have a fully miniaturized system under development in association with our collaborators at Drexel. Initial designs for optical transmitter and receiver have been implemented and the functionality of each module has been verified experimentally. Quad vertical cavity surface emitting laser diodes are used in the transmitter, and the system takes advantage of Gradient-Index (GRIN) lens technology to achieve excellent optical collection efficiency. We are currently working on the integration of the modules. These projects will combine to produce fully wearable DOI for Near Infrared functional imaging. Our theoretical research is also examining motion artifact as a signal instead of noise. Initial results suggest that if we can model the motion of our imaging system relative to the subject via the helmet interface (a process being worked on by our instrumentalists), we should further be able to enhance optical signals to an unprecedented level of accuracy and quantitation in the field. Finally we have submitted and received an initial patent to a novel instrument design intended to detect hematomas. It is designed to assist in the triage of patients with all forms of TBI. The ability to identify and triage for the presence of hematoma would greatly increase efficiency of use of more expensive and limited access systems such as CT and MRI. Currently we are working on the full theoretical model to test the design. Once complete this model will allow us to progress rapidly to an initial prototype. The current status-quo in NIR modeling is also being challenged by this project. Initial results indicate that the paradigm that more sources and detectors at higher density is better for imaging is being challenged. Initial results from this project suggest there will be a fine balance between improved instrumentation and error introduced by the computational boundaries of modeling.